Water-based patches containing, as an active ingredient, ketoprofen that has an anti-inflammatory activity are well known. However, ketoprofen has low water-solubility. Therefore, when a water-based patch contains ketoprofen, a specific solubilizer such as crotamiton, a fatty acid, a fatty acid ester, an essential oil, a polyhydric alcohol, or a surfactant is often used as a solubilizer for the poorly soluble drug (Patent Documents 1 and 2). However, to produce such a patch, some contrivance must be adopted in its production method. Therefore, this production method has a fundamental drawback of low working efficiency during production.
Specifically, many of such specific solubilizers used to solubilize ketoprofen are generally lipophilic solvents. Therefore, such a solvent must be carefully added when a water-based patch is produced. Otherwise, an unfavorable influence may be exerted on the properties of the patch, for example, insolubilization of a water-soluble polymer compound or separation of the lipophilic solvent.
Commonly used water-based patches often contain a polyhydric alcohol such as glycerin at a high concentration. However, when the drug added is ketoprofen that has a carboxylic acid group, an esterification reaction proceeds between the ketoprofen and a solubilizer having a hydroxyl group such as a polyhydric alcohol (for example, glycerin), a lower alcohol, or menthol even at relatively low temperature with a weak acid such as an organic acid or polyacrylic acid, which is a base component of the water-based patch and serves as a catalyst. This results in a problem of low storage stability.
To solve this problem, it is proposed that stabilization of ketoprofen having a carboxylic acid group in its molecule is achieved by dispersing a nonsteroidal anti-inflammatory analgesic containing the ketoprofen in glycerin and glycol having 3 to 30 carbon atoms (Patent Document 3).
However, even in the patch described in this Patent Document, the glycerin used as the base of the water-based patch is an essential ingredient, and therefore it is feared that long-term storage stability will deteriorate due to an esterification reaction. Generally, if a drug is dispersed in a patch, its storage stability is improved, but the drug in the dispersed state results in a reduction in its transdermal absorbability. Therefore, there is a demand for a water-based patch that provides both high storage stability and high transdermal absorbability.
The solubility of ketoprofen in many of patch bases contained in commonly used oil-based patches is high. In addition, many of fatty acid esters, essential oils, crotamiton, etc. used as solubilizers for ketoprofen generally have high compatibility with ketoprofen.
Therefore, an oil-based patch containing ketoprofen provides high transdermal absorbability, and the properties of such an oil-based patch can be maintained without adding a polyhydric alcohol thereto, so that high stability of ketoprofen can be achieved.
Because of the above-described reason, a large number of inventions have been made on oil-based patches containing ketoprofen (Patent Documents 4 and 5), and a large number of products of such oil-based patches have been distributed in the actual pharmaceutical market. However, one problem of the oil-based patches is stimulation to the skin, and it is an object to provide safer products.